From the Department of Ophthalmology (SN, MM, TI), Tokyo Medical University, Ibaraki Medical Center, Ami, Japan; the Computational Optics and Ophthalmology Group (SN, MM, SM, YY), Tsukuba, Japan; the Computational Optics Group (SM, YY), University of Tsukuba, Tsukuba, Japan; and the Department of Ophthalmology (HG), Tokyo Medical University, Tokyo, Japan.
Supported in part by the Japan Science and Technology Agency through the Development of Systems and Technology for Advanced Measurement and Analysis program.
Dr. Miura is on the speaker’s bureau of Novartis and Pfizer. Drs. Makita and Yasuno have received royalties from Tomey Corporation. The remaining authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Masahiro Miura, MD, PhD, Department of Ophthalmology, Tokyo Medical University, Ibaraki Medical Center, 3-20-1 Chuo, Ami, Inashiki, Ibaraki 300395, Japan. E-mail: email@example.com
Polypoidal choroidal vasculopathy (PCV) is characterized by numerous recurrent, bilateral, asymmetric, serosanguineous detachments in the retinal pigment epithelium (RPE).1 Optical coherence tomography (OCT) has been an essential diagnostic tool for the clinical evaluation of PCV.2 However, commercially available OCT systems use an 840-nm wavelength band light source and have limited ability to visualize the deep retinal lesions of PCV. Alternative OCT techniques have reportedly obtained images of deep retinal lesions with enhanced contrast. One technique is enhanced depth imaging (EDI)-OCT.3 Another is OCT with a 1.0-μm band light source, the so-called high-penetration (HP)-OCT.4 Both EDI-OCT and HP-OCT were reported to be useful in imaging sub-RPE lesions.3–5 Better visualization of sub-RPE lesions might be expected by use of a combination of HP-OCT and EDI-OCT (HP-EDI-OCT), which we used in this study to evaluate sub-RPE lesions of PCV.
Design and Methods
We prospectively evaluated 5 eyes of 5 patients (4 men and 1 woman) with PCV (Table). Their ages ranged from 61 to 85 years, and the mean age was 70.6 years (Table). All eyes had mild to moderate nuclear cataract (NC2 or NC3 in Lens Opacities Classification System III).6 A clinical diagnosis of PCV was made after orange-red subretinal lesions and polypoidal lesions were identified by fundus examination and indocyanine green angiography (ICGA), respectively (Figs. 1A, 1B, 1C, 2A, and 2B). All studies were performed according to the tenets of the Declaration of Helsinki and were approved by the institutional review boards of the University of Tsukuba and Tokyo Medical University. Informed consent for the examination was obtained from all subjects.
Table: Patient Characteristics
Figure 1. The left eye of a 63-year-old man exhibited decreased visual acuity. A color fundus photograph (A) shows multiple hemorrhagic pigment epithelium detachments (black arrowhead) with orange-red spots in the macula (white arrowhead). On the indocyanine green angiography images, a branching vascular network was clearly observed in the early phase (B) and polypoidal lesions adjacent to the vascular network were readily observed in the late phase (C). The white line indicates the scanning line of optical coherence tomography (OCT) images (D, E, and F). In the high-penetration enhanced depth imaging OCT image (D), a branching vascular network (white arrowhead), a polypoidal lesion (black arrow), and subretinal pigment epithelium (RPE) hemorrhage (*) were clearly observed. The chorioscleral interface was readily visualized (black arrowhead). On both high-penetration OCT (E) and OCT at 840-nm images without image averaging (F), these sub-RPE lesions were depicted as blurred, low-contrast structures; however, high-penetration OCT images without image averaging displayed better contrast of sub-RPE lesions than OCT at 840-nm images without image averaging.
Figure 2. The left eye of a 63-year-old man exhibited decreased visual acuity. A color fundus photograph (A) shows serous retinal detachment (black arrowhead) with orange-red spots in the macula (black arrow) and a small subretinal pigment epithelium (RPE) hemorrhage (white arrow). The white line indicates the scanning line of optical coherence tomography (OCT) images (C, D, and E). The late phase of the indocyanine green angiography image (B) shows 3 polypoidal lesions (black arrow). High-penetration enhanced depth imaging OCT imaging (C) reveals polypoidal lesions (black arrow) and sub-RPE hemorrhage (white arrow). On both high-penetration OCT (D) and OCT at 840-nm images without image averaging (E), these sub-RPE lesions were depicted as blurred, low-contrast structures; however, high-penetration OCT images without image averaging displayed better contrast of sub-RPE lesions than OCT at 840-nm images without image averaging.
We used a prototype spectral-domain OCT system built by the Computational Optics Group of the University of Tsukuba. A superluminescent diode laser with a central wavelength of 1,020 nm and a band width of 100 nm was used as the light source. The measurement speed was 47,000 depth scans/s, and the depth resolution was 4.3 μm in tissue. Each OCT image consisted of 1,500 A-scans corresponding to 6 mm of the retina, and the zero-delay line was adjusted to be within the inner choroid and the sclera as a standard EDI configuration.3 HP-EDI-OCT images were obtained by averaging 50 B-scan images. We compared the HP-EDI-OCT images, HP-OCT images without image averaging, and commercially available OCT images without image averaging with regard to the visualization of PCV lesions. We used Topcon 3D-1000 (Topcon, Tokyo, Japan) as a commercially available OCT system (central wavelength: 840 nm, axial resolution: 6.0 μm, scanning speed: 18,000 depth scans/s), and each OCT image consisted of 1,024 A-scans corresponding to 6 mm of the retina.
In all eyes, HP-EDI-OCT provided images of sub-RPE lesions with better contrast than OCT without image averaging. The undulating RPE line and a hyper-reflective smooth line representing Bruch’s membrane were clearly visible in the area of the PCV vascular lesions in ICGA images (Figs. 1D and 2C). In the space between the RPE line and Bruch’s membrane, various PCV lesions were identified (Table; Figs. 1D and 2C). Moderately hyperreflective masses were widely distributed in the space between the RPE line and Bruch’s membrane in 4 eyes, and their distribution was consistent with the area of the branching vascular network. Polypoidal lesions were detected as saccular aneurysms within the protruded RPE detachment in all eyes. Sub-RPE hemorrhage was observed as distinct hyperreflective masses in 3 eyes, and fluid spaces were observed as hyporeflective areas in 2 eyes. The chorioscleral interface was clearly observed in all eyes, and the entire structure of the choroid was readily identified (Figs. 1D and 2C).
In the commercially available OCT images without image averaging, image quality was relatively poor with the presence of nuclear cataract and sub-RPE structures were depicted as blurred, low-contrast structures, which made the discrimination of each structure difficult (Table; Figs. 1F and 2E). The visibility of sub-RPE lesions in HP-OCT images without image averaging was better than that in commercially available OCT images despite the presence of nuclear cataract, and HP-EDI-OCT images displayed better contrast of sub-RPE lesions than HP-OCT images without image averaging (Table).
In this study, we used HP-EDI-OCT to evaluate PCV vascular lesions. HP-EDI-OCT provided high-contrast images of sub-RPE lesions of PCV, and various structures were clearly identified in the space between the RPE and Bruch’s membrane.
Commercially available OCT at 840 nm is widely used to evaluate exudative macular diseases, including those of PCV; however, its ability to image sub-RPE lesions is limited. The penetration of an 840-nm light into the deeper tissue of the eye beyond the RPE is relatively poor, making it difficult to obtain images of PCV lesions located beneath the RPE.7 The image quality of OCT at 840 nm deteriorates in the presence of a cataract. In this study, we used HP-OCT with a 1.0-μm band light source. Light at this wavelength is absorbed less by the RPE8–10; hence, HP-OCT is expected to be a suitable tool for obtaining images of structures deeper than the RPE. The image quality of HP-OCT deteriorated less in the presence of nuclear cataract.4 For the commercially available OCT at 840 nm, EDI-OCT by multiple B-scan averaging was used for better visualization of sub-RPE lesions.3 In this study, we used a combination of HP-OCT and EDI-OCT and expected a summation effect. Polypoidal lesions in PCV were observed as hyporeflective masses on HP-EDI-OCT images and were readily distinguishable from branching vascular networks. This HP-EDI-OCT finding corresponded with a histological study that showed polypoidal lesions as thin-walled saccular aneurysms.11 Sub-RPE hemorrhage and adjacent fluid spaces were also clearly identified on HP-EDI-OCT images. These findings on HP-EDI-OCT images could provide a detailed evaluation of PCV vascular lesions, and HP-EDI-OCT might be useful for the diagnosis and clinical assessment of PCV. The detection of these vascular lesions is useful for the diagnosis of PCV,2 and the regression of these lesions is an important marker of treatment efficacy.12–14 As mentioned above, HP-EDI-OCT could detect only some parts of the PCV vascular lesions; hence, ICGA is still required to more thoroughly evaluate the entire structure of PCV vascular lesions. However, the clinical applications of ICGA are limited because of the possibility of severe complications and patient discomfort.15 HP-EDI-OCT is expected to serve as a complementary tool to ICGA for the clinical assessment of PCV.
A limitation of the studies is the lack of comparison between EDI-OCT at 840 nm and HP-EDI-OCT. In OCT images without image averaging, HP-OCT could provide better contrast of sub-RPE lesions than OCT at 840 nm (Table). In the preliminary studies, better visibility of sub-RPE lesions in HP-EDI-OCT images than in EDI-OCT at 840-nm images was reported.16 Further investigation is required to compare HP-EDI-OCT and EDI-OCT at 840 nm.
Controversies exist about the location of PCV vascular lesions.2,17 Some OCT studies speculate that the lesions are located in the space between the RPE and Bruch’s membrane.11,18,19 Other OCT studies speculate that they are located in the choroid,20 and thickening of the choroid in PCV has been reported.21,22 HP-EDI-OCT images revealed the presence of PCV lesions between the RPE and Bruch’s membrane. This feature coincides with the findings of Doppler OCT,23 although this does not necessarily mean that all PCV lesions exist only between the RPE and Bruch’s membrane. However, there is no doubt that the space between Bruch’s membrane and the RPE is a crucial region for pathophysiological changes in PCV.
HP-EDI-OCT is a noninvasive method of imaging various structures of PCV vascular lesions. It also has potential as a noninvasive technique for assessing other macular diseases, including age-related macular degeneration. However, HP-EDI-OCT is still in the developmental stage and is not yet commercially available. Further research is necessary to elucidate the clinical applications of HP-EDI-OCT.
- Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990;10:1–8. doi:10.1097/00006982-199001010-00001 [CrossRef]
- Laude A, Cackett PD, Vithana EN, et al. Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease?Prog Retin Eye Res. 2009;29:19–29. doi:10.1016/j.preteyeres.2009.10.001 [CrossRef]
- Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146:496–500. doi:10.1016/j.ajo.2008.05.032 [CrossRef]
- Yasuno Y, Miura M, Kawana K, et al. Visualization of sub-retinal pigment epithelium morphologies of exudative macular diseases by high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci. 2009;50:405–413. doi:10.1167/iovs.08-2272 [CrossRef]
- Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol. 2009;147:644–652. doi:10.1016/j.ajo.2008.10.005 [CrossRef]
- Chylack LT Jr, Wolfe JK, Singer DM, et al. The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group. Arch Ophthalmol. 1993;111:831–836. doi:10.1001/archopht.1993.01090060119035 [CrossRef]
- Ojima Y, Hangai M, Sakamoto A, et al. Improved visualization of polypoidal choroidal vasculopathy lesions using spectral-domain optical coherence tomography. Retina. 2009;29:52–59. doi:10.1097/IAE.0b013e3181884fbf [CrossRef]
- Povazay B, Bizheva K, Hermann B, et al. Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm. Opt Express. 2003;11:1980–1986. doi:10.1364/OE.11.001980 [CrossRef]
- Unterhuber A, Povazay B, Hermann B, Sattmann H, Chavez-Pirson A, Drexler W. In vivo retinal optical coherence tomography at 1040 nm: enhanced penetration into the choroid. Opt Express. 2005;13:3252–3258. doi:10.1364/OPEX.13.003252 [CrossRef]
- Yasuno Y, Hong Y, Makita S, et al. In vivo high-contrast imaging of deep posterior eye by 1-microm swept source optical coherence tomography and scattering optical coherence angiography. Opt Express. 2007;15:6121–6139. doi:10.1364/OE.15.006121 [CrossRef]
- Lafaut BA, Aisenbrey S, Van den Broecke C, Bartz-Schmidt KU, Heimann K. Polypoidal choroidal vasculopathy pattern in age-related macular degeneration: a clinicopathologic correlation. Retina. 2000;20:650–654.
- Gomi F, Sawa M, Sakaguchi H, et al. Efficacy of intravitreal bevacizumab for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2007;92:70–73. doi:10.1136/bjo.2007.122283 [CrossRef]
- Maruko I, Iida T, Sugano Y, Saito M, Sekiryu T. Subfoveal retinal and choroidal thickness after verteporfin photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2011;151:594–603. doi:10.1016/j.ajo.2010.10.030 [CrossRef]
- Gomi F, Sawa M, Wakabayashi T, Sasamoto Y, Suzuki M, Tsujikawa M. Efficacy of intravitreal bevacizumab combined with photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2010;150:48–54. doi:10.1016/j.ajo.2010.02.008 [CrossRef]
- Yannuzzi LA, Rohrer KT, Tindel LJ, et al. Fluorescein angiography complication survey. Ophthalmology. 1986;93:611–617.
- Yasuno Y, Makita S, Tamada D, Miura M, Ikuno Y. Super enhanced depth imaging of choroid by high-penetration optical coherence tomography. ARVO Meeting Abstracts. 2010:2507.
- Lim TH, Laude A, Tan CS. Polypoidal choroidal vasculopathy: an angiographic discussion. Eye. 2010;24:483–490. doi:10.1038/eye.2009.323 [CrossRef]
- Costa RA, Navajas EV, Farah ME, Calucci D, Cardillo JA, Scott IU. Polypoidal choroidal vasculopathy: angiographic characterization of the network vascular elements and a new treatment paradigm. Prog Retin Eye Res. 2005;24:560–586. doi:10.1016/j.preteyeres.2005.01.001 [CrossRef]
- Tsujikawa A, Sasahara M, Otani A, et al. Pigment epithelial detachment in polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007;143:102–111. doi:10.1016/j.ajo.2006.08.025 [CrossRef]
- Iijima H, Imai M, Gohdo T, Tsukahara S. Optical coherence tomography of idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol. 1999;127:301–305. doi:10.1016/S0002-9394(98)00411-5 [CrossRef]
- Chung SE, Kang SW, Lee JH, Kim YT. Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration. Ophthalmology. 2011;118:840–845. doi:10.1016/j.ophtha.2010.09.012 [CrossRef]
- Koizumi H, Yamagishi T, Yamazaki T, Kawasaki R, Kinoshita S. Subfoveal choroidal thickness in typical age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol. 2011;249:1123–1128. doi:10.1007/s00417-011-1620-1 [CrossRef]
- Miura M, Makita S, Iwasaki T, Yasuno Y. Three-dimensional visualization of ocular vascular pathology by optical coherence angiography in vivo. Invest Ophthalmol Vis Sci. 2011;52:2689–2695. doi:10.1167/iovs.10-6282 [CrossRef]
|Case||Age (Y)||Gender||Eye||Cataract (LOCSIII)||HP-EDI-OCT Findings|
|Polypoidal Lesion||Vascular Network||Sub-RPE Hemorrhage||Fluid Space|